i schriften 1 reihe nr. 112
Transcription
i schriften 1 reihe nr. 112
H ISSN 0933-050 X IINIGUNG AUTOMOBILTECHNIK EV i I SCHRIFTEN 1 REIHE NR.112 Bewertung epidemiologischer Untersuchungen über Dieselmotorabgas und Lungen- und Blasenkrebs - Kritische Übersicht - On the Epidemiology of Diesel-Exhaust and Lung and Bladder Cancer - A Critical Review - Bewertung epidemiologischer Untersuchungen über Dieselmotorabgas und Lungen- und Blasenkrebs - Kritische Übersicht - On the Epidemiology of Diesel-Exhaust and Lung and Bladder Cancer - A Critical Review - Auftraggeber: Forschungsvereinigung Automobiltechnik e.V. (FAT) Contractor / Auftragnehmer: Professor Dr. Ernst L. Wynder Authors / Verfasser: Prof. em. Dr. I.T.T. Higgins, University of Michigan; Dr. R.E. Harris, Ohio State University; Prof. Dr. E.L. Wynder, American Health Foundation Postanschrift: Postfach 170563 • 60079 Frankfurt Telefon (069) 7570-1 Drahtanschrift: Autoverband Telex 411293 Druckerei Henrich GmbH Schwanheimer Straße 110 60528 Frankfurt am Main Vervielfältigung, auch auszugsweise, nur mit ausdrücklicher Genehmigung der FAT VORWORT Seit ihrer Gründung im Jahre 1972 ist die FAT bestrebt, die Zusammenhänge zwischen Automobilabgas und Ökologie und menschlicher Gesundheit zu klären. Sie hat deshalb eine Reihe von Forschungsvorhaben initiiert, Mittel für die Finanzierung beschafft und die Forschungsnehmer bei der Bearbeitung der Projekte durch die Mitglieder ihres Arbeitskreises 1 'Auto und Umwelt', die im Anhang namentlich genannt sind, betreut. Nachdem sich herausgestellt hat, daß Ottomotorabgas in der Atemluft auch in den höchsten darstellbaren Konzentrationen zu keinerlei Tumoren in der sehr empfindlichen Rattenlunge führt, wie im FAT-Projekt Nr. 55 nachgewiesen wurde, sind Untersuchungen über den Zusammenhang von Dieselmotorabgas und Lungenkrebs immer mehr in den Mittelpunkt der Abgaswirkungsforschung gerückt. Zur weiteren Untersuchung dieser Zusammenhänge wurden kürzlich bei neuen Inhalationstests Ratten und Mäuse im 'in-vivo Verfahren' einer mit Dieselmotorabgas und inertem Staub belasteten Atmosphäre exponiert (Schriftenreihe Ökologische Forschung des Bundesministers für Forschung und Technologie: Auswirkungen von Dieselmotorabgasen auf die Gesundheit', 1992). Die Ergebnisse zeigen, daß - es sich bei den aufgetretenen Lungenschädigungen um einen rattenspezifischen Effekt handelt: bei anderen Tierarten sind derartige Effekte nicht aufgetreten. - für Lungenschädigungen mit hoher Wahrscheinlichkeit ein KonzentrationsSchwellenwert an Partikeln überschritten sein muß. Tumoren sind auch bei Ratten nur bei sehr hohen Abgaskonzentrationen aufgetreten. - Dieselruß und inerter Feinstaub gleichermaßen wirken, - die Dieselruß- bzw. Staubpartikel selbst und nicht die angelagerten Kohlenwasserstoffe die gesundheitsschädigende Wirkung ausüben. Um die Übertragbarkeit dieser Ergebnisse auf den Menschen zu klären, werden epidemiologische Untersuchungen durchgeführt, obwohl diese Verfahren große Fehlerquellen in sich bergen. Epidemiologischen Untersuchungen sind besonders aufwendig, weil hierbei eine große Anzahl von Personen und deren Lebensgewohnheiten über eine längere Zeit beobachtet und bewertet werden muß. Deswegen sind auch die epidemiologischen Erkenntnisse oft mit großen Unsicherheiten behaftet, den bei längerer Beobachtungsdauer können leicht Fehler auftreten, weil die Belastungskennwerte in der Regel nicht eindeutig ermittelt und Zusatzbelastungen oft nicht erkannt werden. Bei bestimmten Eigeninteressen der Versuchspersonen werden bewußt oder unbewußt falsche Angaben, z.B. zu den Rauchgewohnheiten gemacht, was die Aussagefähigkeit der Untersuchungen weiter verringert. Wegen dieser Unwägbarkeiten und der vielen möglichen Fehlerquellen hat die FAT darauf verzichtet, eigene epidemiologische Untersuchungen durchzuführen. Sie hat jedoch Prof. Dr. Wynder, Direktor der American Health Foundation, New York, einen durch zahlreiche grundlegende Arbeiten ausgewiesenen Epidimiologie-Experten, gebeten, die Aussagefähigkeit und statistische Gültigkeit der Ergebnisse aus bereits abgeschlossenen epidemiologischen Untersuchungen über den Zusammenhang zwischen Dieselmotorabgas und Lungenkrebshäufigkeit beim Menschen zu bewerten. Herr Professor Wynder bestätigt, daß es nicht möglich ist, die Belastungen einer Versuchsgruppe und einer Kontrollgruppe von Menschen hinreichend genau zu bestimmen. In vielen Fällen werden die fehlenden Daten durch Interpolationen und Erfahrungswerte ersetzt, was zwangsläufig zu Fehlinterpretationen der Ergebnisse führen muß. Trotzdem wird in letzter Zeit die Einführung verschärfter Grenzwerte für die Emission und Immissionen von Dieselpartikeln mit den Ergebnissen aus epidemiologischen Studien begründet. Diese Politik birgt jedoch die große Gefahr, daß Belastungs- und Umweltschutzgrenzwerte aufgrund wissenschaftlich nicht abgesicherter Erkenntnisse festgelegt werden. Die hier vorgelegte Bewertung der zur Frage der Wirkung von Dieselmotorabgas auf die menschliche Gesundheit durchgeführten epidemiologischen Studien macht diese Problematik sehr deutlich. Bei keiner Untersuchung konnte die durch Dieselmotorabgase verursachte Belastung der Atemluft exakt bestimmt werden, weil immer weitere, z.T. größere Einflußfaktoren erkennbar waren, aber nicht bewertet werden konnten. Hier ist vor- allem der Einfluß des Rauchens entscheidend: er kann nicht sicher korrigiert werden. Mit dem Ziel, die Originalbewertungen der Forschungsnehmer zu den einzelnen Studien bekannt zu machen, hat sich die FAT entschieden, den Bericht in Originalfassung, d.h. in englischer Sprache zu veröffentlichen und so den Interpretationsspielraum eng zu halten und Übersetzungsungenauigkeiten zu vermeiden. Die Autoren folgern, daß die von ihnen geprüften epidemiologischen Studien keine lungenkrebserzeugende Wirkung von Dieselabgas nachweisen können. Allen angeblichen Nachweisen fehlt die überzeugende statistische Aussagekraft. FORSCHUNGSVEREINIGUNG AUTOMOBILTECHNIK EV (FAT) Frankfurt am Main, im Juni 1994 Inhaltsverzeichnis / Contents Seite Zusammenfassung 1 Abstract 2 Introduction 3 Relationship between Diesel exhaust exposure and lung cancer 5 Relationship of Diesel exhaust exposure to bladder cancer 18 Acknowledgements 29 References 31 Table 1 : Smoking habits by occupational group 37 Table 2: Lung cancer risk and employment in occupations associated with exposure to Diesel emissions 38 Addresses of authors 39 Mitglieder des FAT-AK 1 'Auto und Umwelt' 41 Zu sammenfassung : Die wichtigste Ursache für Lungen- und Blasenkrebs ist das Rauchen. Auch eine Anzahl von entsprechenden krebserzeugenden Arbeitsstoffen ist eindeutig bekannt. In dieser Studie soll die Frage untersucht werden, ob die übliche Luftverschmutzung und insbesondere die Abgasemission von Dieselmotoren das Risiko für Lungen- bzw. Blasenkrebs erhöhen kann. Dieselabgas hat im Tierversuch nur bei der Ratte - nicht bei Hamster und Maus - dann Krebs erzeugt, wenn es in sehr hohen Dosen verwendet wurde. Die Übertragbarkeit von solchen Versuchsergebnissen vom Tier auf den Menschen ist unsicher, da neben dem Speziesunterschied auch zu berücksichtigen ist, daß der Mensch selbst unter sehr ungünstigen Bedingungen einer viel geringeren Dosis ausgesetzt ist. Bei epidemiologischen Studien zur Wirkung von Dieselabgas treten grundsätzlich 3 Probleme auf: 1. es gibt keine eindeutigen Meßgrößen für die Belastung der untersuchten Bevölkerungsoder Berufsgruppen mit Dieselabgas 2. es ist äußerst schwierig, die Hauptursache dieser beiden Krebsarten, nämlich das Rauchen, quantitativ zu berücksichtigen 3. es gibt bei Ursache / Wirkung-Verknüpfungen starke Vorurteile Viele Studien zum Zusammenhang einer realen oder vermuteten Belastung durch Dieselabgas mit Lungen- bzw. Blasenkrebs haben den Einfluß der Hauptursache, also des Rauchens, völlig außer acht gelassen. In dieser Arbeit wird nachgewiesen, daß die Rauchgewohnheiten bei verschiedenen Berufsgruppen stark voneinander abweichen. Epidemiologische Studien, welche den Einfluß der Rauchgewohnheiten berücksichtigen wollten ,taten das nur für die wichtigsten Unterschiede. Sie ließen viele andere Einflußmöglichkeiten des Rauchens unberücksichtigt, die jedoch das Krebsrisiko beträchtlich erhöhen können. Auch eine angemessene Berücksichtigung anderer verfälschender Einflüsse gelang bisher nicht. Diese Fehlerquellen müssen das Ergebnis epidemiologischer Studien immer dann besonders beeinflussen, wenn der untersuchte Zusammenhang von Ursache, z. B. Dieselabgas, und Wirkung, z. B. Lungenkrebs, nur schwach ist. Die wichtigen epidemiologischen Studien zu Dieselabgas wurden in dieser Arbeit kritisch geprüft. Die Autoren kommen zu dem Schluß, daß keine dieser Studien an belasteten Arbeitsplätzen ein eindeutig erhöhtes Risiko für Lungen- bzw. Blasenkrebs durch Dieselabgas nachweist. Die Ergebnisse dieser Studien zeigen unter den Randbedingungen der epidemiologischen Möglichkeiten, daß ein derartiges Risiko wahrscheinlich nicht existiert. Abstract Cigarette smoking is the most important cause of lung and bladder cancer. known. A number of occupational carcinogens are also well The question whether general air pollution and specifically diesel exhaust emissions increase the risk of these two types of cancer is less certain. Diesel exhaust emissions have produced cancers experimentally in animals when administered in very high dosages, but the relevance of such experiments to man, exposed even under the worst conditions to very much lower dosages, is uncertain. The problems with regard to diesel exposures in man are first that we do not have any very good objective measurements of diesel exposures; second, that i t i s very difficult to allow adequately for the major risk factor of these two cancers, namely, cigarette smoking; and third, that there are powerful inducements towards biased ascertainment. Evidence is presented that smoking characteristics vary greatly in different occupations. Many studies of diesel (or suspected diesel) exposure in relation to lung and bladder cancer have not considered smoking at a l l . Those that have, have often considered only major differences in habits and ignored many other aspects of smoking, which may considerably increase carcinogenic risk. The main epidemiological studies considering diesel exhaust emissions in relation to lung and bladder cancer are c r i t i c a l l y reviewed. Our conclusion is that any increase in the risk of lung or bladder cancer from current exposures to diesel exhaust emissions cannot be large and may indeed not exist. Adequate allowance for other confounding factors has not yet been achieved. Introduction The true relationship between an environmental factor and a disease may be obscured in a number of ways. The most important problems that need to be considered are: case/control selection, confounding by one or more factors having similar effects, biased ascertainment of the data, and the choice of inappropriate subgroups for comparisons. These factor, always matters for concern, become particularly troublesome when the association being sought is weak, that i s , one that increases risk by three-fold or less. In these circumstances sound judgement becomes crucial if conclusions are to be avoided (1-5) . false There have been several reviews of diesel exposure and health effects, especially lung cancer (6-13). In this paper we review the evidence on the relationship between exposure to diesel exhaust emissions and the occurrence of cancer of the lung and of cancer of the urinary bladder, with particular reference to the confounding influence of smoking. Smoking is the major risk factor for both lung and bladder cancer, and i t is obvious that if the data are not adequately adjusted for tobacco exposure, conclusions about the risk of diesel exhaust exposure are likely to be misleading. The difficulties of adjusting adequately for smoking are not enough appreciated. Apart from any differences that exist between smokers and nonsmokers, the number of cigarettes smoked per day, the age of starting to smoke, the total duration of smoking, the quality of the cigarettes smoked (notably their tar content and degree of f i l t r a t i o n ) , and the manner of smoking may all contribute significantly to confounding of occupational exposure by tobacco smoke. Table 1, i l l u s t r a t e s differences between different occupational groups in respect to these factors. The table shows that the lifelong exposure to cigarette smoke of truck drivers in particular differed strikingly from that of a l l other occupations. Fewer truck drivers had never smoked, and of those who had smoked, fewer had used filter-tipped cigarettes, more had smoked heavily, and more had used high-tar cigarettes. The result is that their lifetime cigarette tar dosage was much higher than that of any other occupational group. Most studies dealing with exposure to diesel exhaust and cancer do not have sufficient information on smoking to permit a thorough analysis of this important factor. Consequently, any conclusions on the risk of diesel exhaust exposure and cancer must inevitably remain tentative. Even studies restricting analyses to nonsmokers, although apparently convincing, are subject to uncertainties about the accuracy of the smoking categorization, as well as to possible other differences between smokers and nonsmokers. In this evaluation, we will not deal in detail with the problem of biases, although it" should be clearly recognized that reports on both diesel exposure and smoking may involve different degree of bias when replies come from patients, healthy persons, from the subjects themselves, or from next-of-kin. Relationship betveen diesel exhaust exposure and lung cancer Emissions from diesel engines have been suspected of carcinogenicity for over thirty years. Doll (14) in a valuable review of the epidemiology of lung cancer at that time commented that certain occupations were interesting because they did not appear to be associated with any materially increased risk. Foremost among these were those industries in which the employees had a special exposure to the fumes of petrol or diesel-driven engines. Doll was impressed that police traffic controllers on duty where exposures to bus and automobile exhaust fumes were high appeared to have no excess risk of lung cancer. In his paper, he cited Kennaway and Kennaway (15) and the Registrar General (16), who had shown that the drivers of horse-drawn vehicles had as high (or higher) standardized mortality ratios for lung cancer as drivers of motor vehicles. He noted that the retrospective studies of lung cancer failed to provide any support for the hypothesis (14, 17-19) , and referred to Raffle's observation (20) in the London busmen of somewhat lower lung cancer mortality rates among drivers and conductors and engineering staff at trolley bus depots than of underground railway workers and engineering staff at bus garages. However, he noted that "these results are not of great significance in relation to diesel engines, as these have not been on the road in large enough numbers for diesel fumes to be expected to have produced any evidence of cancer - even if they were capable of doing so." The early studies of diesel exhaust emissions (20-22) appeared to be essentially negative, although the inadequate latency, noted by Doll, limited conclusions from a l l these studies. The London Busmen study, particularly in the follow-up presented by Waller (23), has been perhaps the most influential of these, especially in Britain. But i t s weaknesses, notably an incomplete follow-up, uncertainty about the degree of exposure to diesel emissions, and the lack of any smoking information leave one in considerable doubt. Heuper (24) noted high lung cancer death rates among transportation workers, which he attributed to exposure to exhausts from gasoline and diesel engines, to petroleum lubricants, and to dust from asphalt roads. He commented that 75% of the lung cancer deaths of transport workers occurred among railroad workers, who constituted only 25% of the group. The basis for this statement is not clear. Interest has continued to focus on transportation workers. Hannunkari and co-workers (25) examined mortality and disability in railroad workers in Finland^ They reported that mortality rates for malignant tumors were higher among engineers than among trainmen or clerks. I t i s not clear how these subgroups differed in respect to diesel exposure, and no allowance was made for any potentially confounding factors, such as smoking or social c l a s s . Howe and co-workers (26) reported on the mortality of 43,826 pensioners of the Canadian National Railroad Company from 1965 to 1977. Exposure to diesel fumes was based on the job held immediately before retirement. Three categories of exposure were used: not exposed, possibly exposed, and probably exposed. Mo attempt was made to validate these categories, and no measurements of diesel exposure were made. A gradient of risk of lung cancer was observed, from 1.00 in those considered not exposed, through 1.20 in those possibly exposed, to 1.30 in those probably exposed. A similar gradient was reported for exposure to coal dust, which, the authors comment, would be expected since those now exposed to diesel fumes would in the past have been exposed to coal dust. Slacking histories were not available, but the authors maintain that smoking could not completely explain their findings. Their reason is not, however, convincing, particularly since the mortality rates for emphysema, a fatal disease most strongly related to smoking, were strongly related to the diesel exposure categories. In the united States, Schenker and co-workers (27) published the results of a pilot study of American railroad workers, in which 2519 male railroad workers aged 45 to 64 with 10 or more years of service on the railroads were selected on the basis of their job classifications. Cause specific mortality was established for those who had.died by 1979. Employees considered to be exposed to diesel fumes had a relative risk of lung cancer of 1.42 (95% CI: 0.45 to 2.39) compared with those not so exposed. No allowance was made for smoking in this study. Further studies of the US railroad industry have been published by Garshick and co-workers (28, 2 9 ) . In the first of these, 15,059 deaths, which occurred among 650,000 railroad workers between March 1, 1981 and February 28, 1982, were studied. certificates were obtained for 87% of these deaths. Death There were 8 1256 deaths from lung cancer. These deaths were compared with two decedent controls, which were randomly chosen from all deaths that did not mention cancer anywhere on the death certificate and that were not due to suicide, accident, or unknown causes. Smoking habits and residential histories were obtained for cases and controls by mailed questionnaires or telephone from the next of kin. Occupational histories were determined from yearly job reports available to the Railroad Retirement Board. Personal exposures were assessed for men in 39 job categories in 4 railroads. Particulate exposures ranged from 9 to 76 ug/m for clerks and station agents (considered to be not exposed) to 83 to 168 ug/m for all diesel-exposed groups and from 87 to 322 ug/m for shopworkers. The results were presented separately for men under 65 years of age and for men aged 65 and over. A clear and consistent effect of cigarette smoking on lung cancer was seen in each age group, but a weak effect of diesel exposure was seen only in the younger men. There was no effect in the older men. The authors summarize the findings: "using multiple conditional logistic regression analysis to adjust for smoking and asbestos exposure, workers aged 64 years of age or younger at the time of death with work in diesel exhaust exposed jobs for 20 years or more had a significantly increased relative odds (OR=1.41, 95% 1.88). CI=1.06, No effect of diesel exhaust exposure was seen in men aged 65 and over." The authors claim that "roughly half of the older workers were unexposed to diesel exhaust and that those exposed had a short duration of exposure." This claim is unconvincing on the basis of the figures presented and could be influenced by the classification of those employed before 1959, who were considered to be unexposed. Moreover, there were only 9 nonsmokers among the younger cancer cases, which together with smoking information from next of kin must raise questions about the adequacy of allowance for smoking. In the second paper by Garshick and co-workers (29) , a cohort of 55,407 white male railroad workers, aged 40 to 64 years in 1959, who started to work for the railroad 10 to 20 years earlier, was selected on the basis of the job held in 1959. followed to December 31, 1980. The cohort was By that time 19,396 deaths had been reported to the Railroad Retirement Board (RRB). certificates were obtained for 17,120 (88.3%). Death Of these, 1,694 (8.7%) were attributed to lung cancer (ICD-8: 162) . Diesel exposure was assessed on the basis of annual job codes, reported to the RRB. Workers with potential asbestos exposure were excluded. Analytic methods were complicated and difficult to understand. Directly standardized ratios for deaths from lung cancer in dieselexposed and unexposed workers were computed for 5-year age groups. In addition, a number of proportional hazard models, time dependent and non-time dependent, were examined. Relative risk of diesel exposure adjusted for age was 1.45 for men aged 40 to 44 and declined to 0.98 for men aged 60 to 64. The term time-dependent model seems to refer to the inclusion or exclusion of the last 5 years of life. If these years were included in the estimates of exposure, there was no evidence of a consistent exposure-duration response relationship. With recent exposure excluded, however, the authors were able to produce some statistically significant 10 relationships, of which, a relative risk of 1.72 (95% CI: 1.27/2.33) for men with 15 years or more exposure might be cited. The main weakness of this paper, apart from the complexity of the analysis, is the lack of any allowance for smoking. The authors have considered the possibility that excess risk of diesel exposure could be due to differences in smoking habits between dieselexposed and unexposed groups, but they have rejected this because they say they found no such differences in a group of 517 railroad workers whom they had surveyed in 1982 for past asbestos exposure. They concluded that occupational exposure to diesel exhaust is associated with a modest excess risk of lung cancer. Members of a heavy construction equipment operators union were studied by Wong and co-workers (30) . The mortality of 34,156 male union members was compared with that of all white males in the United States. The Standardized Mortality Ratio (SMR) for all causes of death was 81, while that for lung cancer was 99. A significantly high ratio of 167 was observed for liver cancer. The risk of lung cancer increased as the interval between the time of first exposure in the industry and the time of death increased. A significantly increased SMR for lung cancer was observed among those who had retired, and the SMR remained elevated when those who had retired early were excluded. The reason for this elevated SMR is not clear. No striking relationship with diesel exhaust exposure and lung cancer was observed. In fact one of the more interesting observations in this study was that lung cancer SMRs were low in all those occupations believed to result in high diesel emission exposures, such as scraper, loader, dozer, or backhoe 11 operator. This study lacks any smoking information. To the extent it provides any sound basis for categorizing diesel exposures, its findings do not suggest there was much risk of lung cancer from diesel exhaust emissions. Boffetta and co-workers (31) reported an analysis of 2-year mortality of 461,981 men aged 40 to 79 enrolled in the American Cancer Society's prospective study, in relation to occupations with likely diesel exhaust exposure. They observed a relative risk adjusted for smoking of 1.05 (0.97, 1.13) for all causes of death and of 1.18 (0.97,1.44) for lung cancer. A dose-response effect was observed, the risks being 0.94 for all causes of death and 1.05 for lung cancer in those with 1 to 15 years exposure, compared with 1.09 and 1.21 in those with 16 years exposure and over, respectively. Railroad workers, heavy equipment operators, miners, and truck drivers had higher mortality rates both from all causes and from lung cancer when compared with subjects with other occupations and no exposure to diesel emissions. However, truck drivers who were exposed to diesel emissions were not at any increased risk of lung cancer when compared with truck drivers who were not exposed to diesel emissions. This suggests that differences other than diesel exposure may have been responsible for the difference in risk of lung cancer between truck drivers and other men. It is interesting to note in this paper that among men classified as having increased diesel exposure significantly raised relative risks were observed for cerebrovascular disease (1.61), arteriosclerosis (3.12) , pneumonia and influenza (1.97) , cirrhosis 12 of the liver (1.79), accidents (1.56), and ill-defined conditions (3.44) . The importance of allowing adequately for smoking in assessing the risk of diesel exhaust exposures was illustrated in a casecontrol study conducted by Hall and Wynder (32) that compared 502 lung cancer cases with 502 controls matched for age, race, hospital, and time of admission. The groups were interviewed for smoking, alcohol *nd coffee consumption, use of artificial sweeteners, occupations held, occupational exposures, and other demographic variables. The expected strong relationship between cigarette smoking and lung cancer was observed. A two-fold increased risk was also observed in those who were exposed to diesel exhaust when no allowance was made for smoking. When due allowance for smoking was made, the excess risk was reduced, and the excess was no longer statistically significant (OR: 1.4, CI:0.8, 2.4). In this study the relative risk of nonsmokers and ex-smokers, combined because of small numbers, was also modestly raised (OR: 1.46 ,CI:O.9 ,2 .3) . In a further study from the American Health Foundation, Boffetta and co-workers (33) compared 2584 lung cancer cases with 5099 hospital controls. The crude odds ratio for those considered probably exposed to diesel exhaust was 1.31 (1.09, 1.57), but when adjustment for smoking and other confounders was made, the estimate was reduced to 0.95 (0.78,1.16). Similar results were obtained for truck drivers, which was the only occupational category large enough for separate analysis. An interesting, additional feature of this study was that when selfreported exposures to diesel emissions were used, rather than more 13 objective estimates derived from occupations held, the crude odds ratio of 1.45 (0.93, 2.27) was reduced to 1.21 (0.78, 2.02), suggesting the possibility of some reporting bias. Steenland and co-workers (34) studied male decedents from the Central States files of the Teamsters union. There were 10,699 deaths in 1982 and 1983 among men who had filed claims for pension benefits, which requires 20 years tenure in the union. certificates were obtained for 10,485 (98%). Death Cases were all deaths from lung cancer (ICD 162,163), either underlying or contributory. Controls were a systematic one in six samples of all 10,485 social security numbers, excluding deaths from lung or bladder cancer and motor vehicle accidents. 1452 controls. There were 1288 lung cancer cases and Occupational histories were obtained from Teamster Union records and supplemented by information obtained from the next of kin. The data were analysed separately for each source. Information on smoking and other confounding factors, such as diet and asbestos exposure, was obtained from the next of kin. Interviews were conducted with the next of kin of 1085 (82%) cases and 1160 (80%) of the controls. After excluding missing information, 77% of the cases and 75% of the controls were available for analysis of occupation using Teamster records, and 68% of the cases and 66% of the controls using next of kin data. Men were classified according to the job category in which they had worked longest (from the next of kin: gasoline truck driver, diesel truck driver, driver of both types of truck, truck mechanic and dock worker; from the Teamster work histories: long-haul, shorthaul, or city drivers, truck mechanics and dock workers). Men who 14 had never worked in any of these job categories were classified as nonexposed, or as men who had held other jobs with potential diesel exposure. Several job categories had raised lung cancer risks compared with unexposed workers, but none of the differences was statistically significant. However, based on the Teamster history, a significant positive trend was observed with increasing years of employment as a long-haul truck driver after 1959 or 1964. Based on the next of kin history, men whc primarily drove diesel trucks showed a similar increasing lung cancer risk with increasing duration of employment; but the trend was not statistically significant, (p=0.12). Long-term drivers of primarily diesel trucks had an odds ratio of 1.89 (1.04, 3.42). The authors have concluded that their results suggest that some types of truck drivers have an increased risk of lung cancer. This excess may be confined to truck driving after 1959 and specifically to diesel trucks. However, they point out that the exposures of truck drivers are unknown and that no measurements were made in this study. This is one of the increasing number of papers being published nowadays in which the reader has no chance of following and checking the analysis. The crude odds ratios are strikingly different from those presented in Table 3, presumably because of the allowances incorporated for age and cigarette smoking. But no data are presented on either of these crucial factors. So the reader has to take what he is told on trust. The main reservation to accepting the findings in this study, however, stem from the 15 difficulty of obtaining adequately detailed and unbiased smoking habits from next of kin. Hayes and co-workers (35) studied the association between employment in motor exhaust-related occupations and lung cancer in three case-control studies carried out by the National Cancer Institute between 1976 and 1983 in Florida, Louisiana, and New Jersey. In all, there were 2291 cases of lung cancer and 2570 controls. Cases and controls were either all male (Florida and New Jersey) or matched for age (Louisiana) . Most of the analyses were limited to subjects who had been personally interviewed. For those with 10 or more years in motor exhaust-related occupations (MER) , the age, smoking and study related adjusted odds ratio for lung cancer was 1.5: (95% CXtl.2-1.9). The risk was raised for both truck drivers and other MER occupations (truck drivers OR: 1.5, 95% CI: 1.1,1.9; other occupations OR: 1.4, 95% CI:1.1,2.0). The 50% increase in risk was not due to differences in race or exposure to recognized carcinogens between the groups and could not be explained by the greater use of cigarettes or by other occupational exposures. The authors were unable to evaluate whether diesel or gasoline engine exposures were more strongly related to the elevated risk observed. The greater risk of lung cancer among those in MER occupations shown in this study is persuasive. Occupations seem to have been as well categorized as is possible in personal interviews. The categorization of smoking habits, however, seems to have been limited to stated cigarettes per day, which we have already suggested is not really adequate to exclude differences between 16 groups. Nevertheless, the observation that an increased risk of lung cancer was present even in nonsmokers provides some evidence that the excess risk was not entirely due to cigarette smoking. Questions about the accuracy of reporting of not smoking, less accurate than is often thought, or of bias between cases and controls, remain as potential sources of error. This study should be considered in the light of the study by Siemiatycki and co-workers (36) . This comprised a populationbased, case-referent study of 3726 cancer patients, aged 30 to 70, in 19 Montreal hospitals. For each cancer site, a reference group was selected from other cancer patients. The odds ratio of patients with squamous cell lung cancer who were categorized as exposed to gasoline exhaust was modestly increased (OR: 1.2, 90% CI:1.0, 1.4). The odds ratio of those exposed to diesel exhaust was similar (OR: 1.2, 90% CI: 1.0,1.5). Thus, in this study, it appeared that a small increase in lung cancer risk might result from either exposure to gasoline or to diesel emissions. However, the validity of categorization into gasoline or diesel exposed may be open to question. No allowance for cigarette smoking was made in this study. Benamou and co-workers (37) analysed occupational exposures in relation to lung cancer in the French component of the international lung cancer case-control study (38) . In this study, 1625 histologically-confirmed cases of lung cancer and 3091 controls, matched for age, sex, hospital admission, and interviewer, were available and 1334 cases (82.1%) and 2409 controls (77.9%) were compared. Information was collected by 17 questionnaire on smoking, drinking, occupation, and residence. A complete occupational history was taken. Since most women had no occupation (sic) and few men had smoked cigars and pipes, the results were limited to male nonsmokers or exclusively cigarette smokers. An excess risk was observed in those classified as transport equipment operators among motor vehicle drivers (International code 985). After adjusting for cigarette smoking, the odds ratio was 1.42, CI:1.07,1.89) . There was no evidence of an increasing risk with increasing duration of exposure, nor was any significant interaction of occupation and smoking found, although the evidence for these two statements is not given. Additional papers on diesel exhaust emissions in relation to lung cancer are summarised in Table 2 (39-46, 48-53). The table shows that many papers reporting significantly increased risks of lung cancer among diesel-exposed workers have often failed to allow for differences in cigarette smoking between the groups. Several studies have shown raised risks when a crude analysis of the data is carried out, but little or no increased risk when the analysis is refined. In some studies in which the risk persists, comparisons within the occupational group have failed to reveal a dose-response relationship. This suggests that some characteristic other than exposure to diesel emissions may differentiate the groups. It should not be concluded from this table that where we have checked that allowance for cigarette smoking was made, it necessarily implies that the allowance was adequate. Indeed, as we have already indicated, a better case can usually be made for the view that it was not. Our present thinking is that inadequate 18 control of confounding by smoking together with conscious or unconscious bias in reporting could easily explain the relatively small risks now often alledged to be due to exposure to diesel exhaust emissions Relationship of diesel exhaust exposure to bladder cancer Apart from cancer of the lung, there has been considerable concern during the past decade that exposure to diesel exhaust emissions might also cause cancer of the bladder. Milham (44), reviewing occupational mortality for the State of Washington, observed elevated proportional mortality ratios for bladder cancer among gas station workers, fuel o i l dealers, garage owners, auto mechanics, fuel o i l or gasoline truckers, taxicab d r i v e r s , truck drivers and deliverymen. review. No allowance for smoking was made in this However, in a study of 24,416 persons admitted to Roswell Park Memorial I n s t i t u t e between 1956 and 1965, Decoufle and coworkers (40) found that after allowing for smoking, there was a modestly increased risk of lung cancer among railroad engineers and firemen and bus- truck- and taxi-drivers; Neither of the two prospective studies of lung cancer conducted on railroad workers in Canada or the United States has provided any evidence on the risk of bladder cancer among workers exposed to diesel exhaust emissions. In the analysis of diesel exhaust exposed occupations among men enrolled in the American Cancer Society's prospective study, referred to earlier (31) , no particular comment was made on bladder cancer. Table 9 from the 19 paper by Boffetta et al.(31), shows that there were 13 deaths from bladder cancer during the two-year period considered. This gives a relative risk adjusted for age, smoking and other occupational exposures of 1.04, which was insignificantly different from unity and does not suggest much increased risk of bladder cancer from diesel exhaust emissions. The number of bladder cancer cases, however, was small, and further analysis of this exposure subgroup after a longer period than two years would be valuable. In the study of heavy equipment operators carried out by Wong and co-workers (30) , the standardized mortality ratios of those having high and low diesel exhaust exposure were almost identical. A large population-based, case-control study of 480 male and 152 female bladder cancer cases was carried out by Howe and coworkers (54) in Canada. A strong effect of cigarette smoking was reported with lower risks in smokers using filter-tip cigarettes. Increased risks were also found in chemical, rubber, photographic, petroleum, medical and food processing industries among men, and in persons exposed to fumes and dust of either sex. Railroad workers and those exposed to diesel and traffic fumes were two groups with increased risks. The authors suggested that this excess risk was most likely to have been due to hydrocarbons in the form of fuel and lubricating oils. Increased risks were also found from coffee drinking and from the use of private water supplies. Two studies, based on the National Cancer Institute's bladder cancer case-control study (55) have been published (56, 57). Silverman and co-workers (56) compared 303 white male bladder cancer cases with 296 age-matched controls from the general 20 study area in D e t r o i t . In both these s t u d i e s , cases aged 21 to 84 were identified through the Surveillance Epidemiology and End Results (SEER) R e g i s t r i e s . Controls under 65 years were obtained by random-digit d i a l i n g , and controls aged 65 and over from the Health Care Financing Administration's population lists. Information was c o l l e c t e d in personal interviews on occupations held and possible exposures, smoking h a b i t s , c o f f e e consumption, a r t i f i c i a l sweetener and hair dye use, and other medical d e t a i l s . The trucking service industry was the only industry with an increased risk of bladder cancer (OR: 2.2 CI: 1 . 1 , 4 . 4 ) . This appears to be a crude r a t i o , unadjusted for smoking, and no evidence i s given that enables the reader to do the adjustment. Within the trucking service industry, s i g n i f i c a n t l y raised risks were found for truck drivers (OR: 2 . 5 , CI: 1 . 4 , 4 . 4 ) and i n s i g n i f i c a n t l y raised risks for deliverymen, OR: 1 . 6 , CI: 0 . 9 , 2 . 6 ) , bus drivers (OR: 1 . 5 , CI: 0 . 4 , 5 . 3 ) , and taxicab drivers and chauffeurs (OR: 2.0,CI: 0 . 7 , 5 . 4 ) . The crude relative risk of 2.5 in the truck drivers was reduced to 2.1 after adjustment for age and cigarette smoking. I t i s not c l e a r whether this remained s i g n i f i c a n t l y elevated since the e f f e c t on the confidence intervals i s not given. The risk increased with duration of exposure. Truck drivers who reported operating v e h i c l e s with d i e s e l engines had a particularly high risk (RR: 1 1 . 9 , 95% C I : 2 . 3 , 61.1). In a later paper (57) , a l l 1909 white male bladder cancer cases and 3569 population-based controls seen during a one-year period during 1977 and 1978 were compared S t r a t i f i c a t i o n of the r e s u l t s was by age, smoking, c o f f e e drinking, employment in other 21 motor exhaust occupations, occupational exposure to known high risk substances, occurrence of urinary tract infections, urbanization and geographical area. Truck drivers or deliverymen, taxicab drivers or chauffeurs, and bus drivers had raised risks of bladder cancer. The risks were higher in those reporting the occupation as their usual occupation than in those who reported ever being so employed. For truck drivers and deliverymen usually so employed, the excess risk was 50%, (OR: 1.5, CI: 1.1,2.0). There was a rather consistent trend of increasing risk among those who reported ever being a truck driver or deliveryman. Both of these studies have potential sources of bias. The proportions of bladder cancer cases inteviewed was lower than that of the controls, and the proportion of proxy interviews was correspondingly higher for the cases than for the controls. Ascertainment bias is always a worry in retrospective studies of this kind since an expected hazard may be more readily reported by proxies. Stratification by so many factors must have been a very difficult task. Its adequacy may be questioned. There is also uncertainty about the degree of exposure of truck drivers to diesel fumes. Some objective measurement of this is badly needed. In a further study of bladder cancer, Hoar and Hoover (58) compared cases and controls who had died in Vermont and New Hampshire during 1975 to 1979. Information was obtained by personal interviews from the next of kin. An increased risk of bladder cancer among truck drivers was found , (OR: 1.5, 95% CI: 0.9, 2.6). The increased risk was unaffected by allowance for smoking and coffee drinking. It is not clear how this allowance 22 was made and the problems of ascertainment bias in this study are serious. Wynder and co-workers (59) compared 194 histologically confirmed bladder cancer cases in 26 hospitals with 582 controls, matched for age, sex, race, hospital, and time of admission. Standardized interviews were obtained on smoking, occupation, coffee and alcohol ingestion and other factors admission. at the time of The risk of bladder cancer among cigarette smokers was found as expected. There was also an increased risk among those patients who were categorized as having high exposure to diesel exhaust emissions (OR: 1.68; 95%CI: 0.49,5.73). This excess was completely eliminated by adequate allowance for cigarette smoking. In a later study from the American Health Foundation, Iyer and co-workers (60) confirmed an apparently increased risk of bladder cancer from exposure to diesel exhaust emissions. In this study crude odds ratio among the diesel exposed group was 1.40, but after allowing for cigarette smoking, the estimate was reduced to 1.2, with 95% CI:0.8, 2.0. Risch and co-workers (61) compared 825 cases of bladder cancer, occurring during the period 1977 to 1982 in four Provinces in Canada, with randomly selected population controls. The histologically verified cases of bladder cancer were individually matched by age, sex, and area of residence with 792 controls. Lifelong occupational and residential histories, past medical experience, intake of certain dietary items, and exposure to tobacco and certain other l i f e style factors was obtained by interviewing the participants in their homes. Analysis was by 23 conditional, logistic regression. After allowing for smoking, most occupational factors examined were not associated with significantly increased risk of bladder cancer. For exposures between eight and twenty eight years before diagnosis, however, men employed for six months or more as t a i l o r s , or in jobs in chemicals and dyeing, pr exposed to tars or asphalt, or in jobs having exposure to diesel or traffic fumes had raised r i s k s . fumes, the odds ratio was 1.68, (p=0.0008) . exposures to such fumes were differentiated I t is not clear if the from exposures to tars and asphalts, nor if diesel fumes were differentiated fumes. For diesel from traffic The authors concluded that jobs having exposure to diesel or traffic fumes appeared to convey s l i g h t l y increased r i s k s . There has been interest in bladder cancer in Denmark for many years. Clemmesen was interested in the association between lung and bladder cancer and devoted one volume of his s t a t i s t i c a l studies to bladder cancer (62) . A comprehensive review of the state of knowledge on bladder cancer was carried out by Lockwood (63). In addition to his excellent review, Lockwood carried out a case-control study in which he compared 369 bladder cancer patients in Kobenhaven, Frederiksberg, with 369 controls (63). One observation is relevant to our present concern. Lockwood reported that there were 14 bladder cancer cases among persons working on railways and tramways, whereas 7.9 cases might have been expected. This gives an excess risk of approximately 1.8. Since the use of diesel trains and trams in Denmark before 1960 must have been infrequent and of short duration, i t seems unlikely that exposure to diesel emissions could have had anything to do with this excess 24 risk and supports the view that there might be other differences between railway and tram workers to account for an increased cancer risk. Jensen and co-workers (64) compared 371 bladder cancer cases with 771 controls, drawn at random from the general community. Previous papers have focussed on smoking, coffee and other beverage consumption. This one presents their findings on drivers, painters, and certain other occupations. After adjustment for age and tobacco smoking, there was an increased risk of bladder cancer in those men engaged in land transport, in particular bus, taxi, or truck driving. Risks increased fairly consistently with increasing duration of employment, suggesting a dose-response relationship. Unfortunately, although adjustments were made for smoking, no smoking data are presented in this paper, and the evidence on smoking and occupational exposure is not shown. There is also the problem of rumination bias in this study, which i s inherent in a l l comparisons of hospital p a t i e n t s , who have frequently been questioned about their smoking habits, with healthy controls, who may never have been asked about their smoking habits and may not be inclined to elaborate on them. Mommsen and co-workers (65) compared 30 determinants of bladder cancer in 165 male bladder cancer patients with a similar number of controls living in a predominantly rural area of Denmark. They reported a significantly increased relative risk associated with cigarette smoking, a history of prostatic surgery, nocturian previous venerial disease, and certain industrial exposures, specifically to o i l , gasoline and certain unspecified chemicals. 25 An insignificantly raised odds ratio was also noted for those with a history of working with petroleum and asphalt. The significance of these occupational exposures, however, is questionable since no allowance seems to have been made for smoking. In Germany, Franzel-Beyme and co-workers (66) compared 531 male bladder cancer patients with 531 matched hospital controls. An increased risk was observed in several occupational sub-groups. The risk was increased in long-distance truck drivers (OR: 1.79, CI: 1.12, 2.83). There was no increase in risk with increasing duration of truck driving. Allowance was apparently made for smoking but i t s adequacy is somewhat questionable. The details are not given in the paper. This study needs to be read in conjunction with an earlier publication from this group of investigators (67) , which compared 431 bladder cancer cases (340 males and 91 females) with a similar number of controls. A clear effect of smoking was observed, and elevated risks were reported for those engaged in a number of industries, notably rubber, p l a s t i c s , dye, t e x t i l e s , mining, spray painting, coal pitch, chromium and zinc. After allowing for smoking, an increased risk of those drinking more than 4 cups of coffee daily, half to one l i t e r of beer daily, or high-proof s p i r i t s was noted. Frequent consumption of canned food and fatty meals were associated with higher r i s k s . A highly significant odds ratio of 4.9 was found for a daily fluid intake of more than 2 liters. The relation of this report to that on the long distance truck drivers is not clear, but presumably both involve the same population and there was considerable overlap. I t is hard to 26 interpret so many positive associations, which may be confounded to a varying degree. Iscovitch and co-workers (68) carried out a case-control study of bladder cancer in the Greater La Plata region of the Argentine with 117 cases of cancer compared with 117 hospital and 117 neighbourhood controls. A strong effect of smoking was reported. In addition, the authors noted a remarkable effect of coffee drinking, odds ratios of 4.45 and 12.0 being reported for those drinking 2 cups per day and three or more cups daily. Odds ratios were also raised in those engaged in truck or railway work even after allowance for smoking. On the basis of the data presented, i t is difficult to calculate odds ratios for occupational exposure after allowing for smoking, since several of the cells had no cases or controls. In addition in assessing the effect of occupation allowing for smoking, no allowance was made for coffee drinking. All in a l l there seems to be considerable potential for residual confounding in the occupational comparisons. Confounding of the effects of occupational exposure by cigarette smoking i s now fairly generally recognized and has been considered in most of the more 'recent studies of diesel exhaust. Other personal factors, that may confound occupational assessments, have seldom been equally thoroughly treated. Much of the evidence indicting diesel exhaust as a cause of lung cancer has resulted from studies, which have found higher lung or bladder cancer risks in truck drivers, who are then assumed to have been exposed to diesel fumes. However, long distance truck drivers not surprisingly have an unusual l i f e s t y l e , spending long hours 27 driving their trucks to and fro across the continent. We have recently compared their l i f e style with that of more representative samples of the population (69) . Interviews were conducted with truck drivers, who stopped at a truck stop in Bloomsbury, New Jersey. The interviews were conducted between October, 1985 and April, 1986, when 206 truck drivers were asked a broad spectrum of questions about their l i f e - s t y l e . Heavy cigarette smoking and coffee consumption were reported. In addition, these truck drivers reported a very high consumption of dairy products, with their consumption of eggs, b u t t e r , margarine and cheese being far greater than comparably aged groups in other occupations. I t is possible that any excess of cancer that these truckers may have could be due more to their unusual l i f e s t y l e than to any occupational exposures. Heavy cigarette smoking i s almost always found in studies of bladder as well as of lung cancer and coffee drinking, although less consistently involved, is fairly generally accepted as being carcinogenic (70) . Dietary fat is not yet generally agreed to play a role in the etiology of lung or bladder cancer, although a role of fats has been suspected by some research workers. Bladder cancer is rare in Japan but increases in Japanese migrants to Hawaii. Moreover, correlation studies between dietary fat and bladder cancer show a moderately positive association, (p=0.58). The views and opinions of an I ARC Working Group, which met in Lyon, June 14-21, 1988, on the evaluation of Carcinogenic Risk to Humans of Diesel and Gasoline Engine Exhaust and Some NitroArenes (71) have recently been published. After reviewing the l i t e r a t u r e , the group concluded that in humans there was limited 28 evidence for carcinogenicity of diesel engine exhaust, inadequate evidence for the carcinogenicity of gasoline engine exhaust, and limited evidence for the carcinogenicity of engine exhaust, unspecified as from diesel or gasoline engines. The group's overall evaluation was that diesel engine exhaust was probably carcinogenic to humans (Group 2a carcinogen) and that gasoline exhaust was possibly carcinogenic to humans (Group 2b). Our conclusion from the literature ih that, although the evidence suggests that truckers and railroad workers with exposure to diesel exhaust may have some increased risk of bladder and possibly of lung cancer, we are not convinced that this increased risk is due to diesel exposure, or that i t is even certainly due to occupation. Personal factors and other exposures have not yet been adequately excluded. 29 ACKNOWLEDGMENTS We are indebted to Dr. Edith Zang, Division of Epidemiology, American Health Foundation, for preparation of Table 1. We thank Mrs. Roz Fieland and Mrs. Clara Horn for their editorial assistance. 31 References; 1. Wynder EL, Higgins ITT, Gordis L (1987); Workshop Report: Workshop on Guidelines to the Epidemiology of Weak Associations. Prev Med 1987; 16:139-212. 2. Stellman SD, Confounding. 3. Feinleib M. Biasses and weak a s s o c i a t i o n s . 16:150-164. 4. Stallones RA. The use and abuse of sub-group a n a l y s i s . 1987; 16:183-194. 5. Schlesselman J J . "Proof" of cause and effect in epidemiologic s t u d i e s . Ibid 1987; 16:195-210. 6. Envijgonmental P r o t e c t i o n Agency. Health e f f e c t s associated with d i e s e l exhaust emissions: L i t e r a t u r e review and evaluation. EPA 600/1-78-063, November, 1978. 7. National Academy of Sciences, National Research Council. 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JNCI 1984; 72:61-65. 54. Howe GR, Burch JD, Miller AB, et a l . Tobacco use, occupation, coffee, various nutrients and bladder cancer. JNCI 1980; 70:237-245. 55. Hoover RN, Strasser PH, A r t i f i c i a l sweeteners and human bladder cancer: Preliminary Results. Lancet 1980; 1:837-840. 56. Silverman DT, Hoover RN, Albert S, et a l . Occupation and cancer of the lower urinary t r a c t in D e t r o i t . JNCI 1983; 70:237-245. 57. Silverman DT, Hoover RN, Mason TJ, et a l . Motor exhaustrelated occupations and bladder cancer. Cancer Research 1986; 46:2113-2116. 58. Hoar SK, Hoover RN. Truck driving and bladder cancer mortality in rural New England. JNCI 1985; 74: 771-774. 59. Wynder EL, Dieck GS, Hall NEL, et a l . A case-control study of diesel exposure and bladder cancer. Environ Res 1985; 37:475489. 60. Iyer V, Harris RE, Wynder EL. Diesel exhaust exposure and bladder cancer risk. Euro J Epid 1990; 6:49-54. 35 61. Risch HA, Burch JD, Miller AB, et al. Occupational factors and the incidence of cancer of the bladder in Canada. Brit. J industr. Med. 1988; 45:361-367. 62. Clemmesen J. Statistical studies in the aetiology of malignant neoplasms IV: Lung/Bladder ratio, Denmark 19431967. Acta Path Bact Scand Suppl 247. Kobenhaven, 1974. 63. Lockwood K, On the etiology of bladder tumors in Kobenhaven, Fredricksberg: An enquiry of 369 patients and 369 controls. Acta Pathol. Microb. Scand. 1961; 145:1-165. 64. Jensen OM, Wahrendorf J, Knudsen JB, Sorensen BL, The Copenhagen case-reference study of bladder cancer. Risks among drivers, painters and certain other occupations. Scand J Work Environ Health 1987; 13:129-134. 65. Mommsen S, Asgaard J, Sell A. An epidemiological casecontrol study of bladder cancer in males from a predominantly rural district. Euro J Cancer Clin Oncol 1982; 18:1205-1210. 66. Frentzel-Beyme R, Chang-Claude Jenny, Kunze E, Fall-KontrollStudien zur Erkennung von beruflichen Factoren fur Blasenkrebs. Soz Praeventivmed 1989; 34:249-255. 67. Claude J, Kunze E, Frentzel-Beyme R, et al. Life-style and occupational risk factors in cancer of the lower urinary tract. Amer J Epid 1986; 124:578-589. 68. Iscovich J, Castaletto R, Esteve J, et al. Tobacco smoking, occupational exposure and bladder cancer in Argentina. Int J Cancer 1987; 40:734-740. 69. Wynder EL, Miller S. Motor exhaust-related occupations and bladder cancer. Cancer Res 1988; 48:1989-1990. 70. Wynder EL, Higgins ITT. Carcinogenic and mutagenic effectsof diesel engine exhaust. Editors: Ishinishi N, Koizumi N, McClellan RO and Stober W. Elsevier Science Publishers, 1986. 71. IARC Monograph no.46 on evaluation of carcinogenic risks to humans of diesel and gasoline engine exhausts and some Nitroarenes, Lyon, 1989. Table 1 . Mean Age at Diagnosis X ± S.D. Never Smoked t Current Smoker Mean # Cigs/Day Mean # Yrs. + % Snoking Habits by Occupational Group S.D. Smoked + S.D. Filter Only* I % Inhale Deeply* Mean Tar ** Lifetime Tar Cig (mg/cig) (kg) X ± S.D. t s .D. Occupation # Physicians 240 57.0 + 10.2 82 34.2 28 11.7 26.3 + 12.4 34.1 ± 11.4 4 14.3 7 (25.0) 12.6 ± 3.9 5.8 ± 3.7 Engineers 387 57.4 ± 9.4 118 30.5 65 16.8 25.1 ± 14.2 35.6 ± 10.9 6 9.2 13 20.0 13.5 + 4.6 5.0 ± 3.4 1642 54,2 + 9.8 422 25.7 402 24.4 28.1 + 16.5 35.0 + 10.8 70 17.4 123 30.6 13.3 + 4.7 6.4 ± 5.1 55.1 ± 10.3 318 24.4 346 26.6 26.6 ± 14.0 35.9 + 11.6 60 17.3 83 24.0 13.5 + 4.6 6.1 3571 55.6 ± 9.6 732 20.5 1247 35.0 26.3 ±14.9 37.8 ± 10.9 150 12.0 347 27.8 13.5 ± 4.8 6.7 ± 4.5 Semi-Skilled 535 55.2 ± 9.1 107 20.0 233 43.5 24.0 + 13.9 37.6 ± 11.0 24 10.3 51 21.9 13.2 ± 4.8 6.4 + 4.0 Taxi/Truck 557 78 14.0 234 41.9 27.0 + 14.4 38.6 ± 10.6 23 9.8 64 27.4 13.9 + 4.9 7.2 ± 5.0 2096 54.9 ±10.3 585 27.9 513 24.5 24.6 ± 15.0 35.2 ± 11.7 94 18.3 114 22.2 13.1 + 5.0 5.5 ± 4.3 Business Executives Sales/Clerical 1303 Skilled Other 55.7 + 9.4 + 4.3 * Current Smokers **Latest Brand Smokeds 00 38 Table 2: Lung Cancer Risk and Employment in Occupations Associated With Exposure to Diesel Emissions AUTHOR DATE Raffle (20) 1957 TYPE OF CONTROL STUDY SMOKING CO N #OF CASES RELATIVE RISK 0.4* OCCUPATIONS 23 22 18 0.9 0.8 Bus Drivers Engineering Staff Bus Conductors Probably inadequate latency Probably inadequate latency Kaplan (21 ) 1959 CO N 49 0.9 Railroad Workers Menck & Henderson (39) 1976 CO N 23 109 28 46 3.4* 1.6* 1.5* Taxi Drivers Truck Drivers Auto Repair Mechanics (excl. auto) - 3.3 Decoufle et al. (40) 1977 ce Y 56 8 6 1.1 1.8 0.8 Truck Drivers Bus Drivers Heavy Equip. Operators ueupker & Smith (41) 1978 CO N 34 1.2* Truck Drivers and Mechanics Williams et al. (42) 1977 ce Y 13 12 1.3 1.4 Truck Drivers Railroad Workers Waller (23) 1980 CO N 259 59 219 0.7 0.9 0.8 Bus Drivers Maintenance Workers Engineers Ahlberg, et al. (43) 1981 ce N 154 1.6* Truck Drivers Milham (44) 1983 PM N 371 72 250 1.1 Truck Drivers Bus Drivers Heavy Equip. Operators 1.5* 1.4* Rushton, et al. (45) 1983 CO N 102 1.0 Garage Workers/ Engineers General hands Morton & Treyve (46) 1982 CO N 64 1.8* Truck Drivers Boffetta, et al. (31) 1988 CO Y 48 1.24 5 2.60 Truck Drivers No D/R? meaning Heavy Equip. Operators 240 1.02 Boffetta, et al. (33) 1990 cc Y 210 114 Steenland, et al. (11) 1990 cc Y 213 Hayes, et al. (35) cc Y 147 14 1989 38 Milne et al. (47) 1983 cc (deaths) N 16 26 4 23 2 1.06 0.92 1.31 0.92 0.95 1.31 0.83 0.88 Possible exposure at work Probable exposure at work Truck Drivers CC = Case/Control Cell Type Analysis Crude Analysis Stratified Analysis Logistic Analysis Crude Analysis Stratified Analysis Logistic Analysis Crude Analysis Stratified Analysis Logistic Analysis 1.55* Long haul truck driver with 18 yrs exposure after 1959 Smoking habits from next-of-kin Linear trend (Coef 0.027) 1.5* Truck Drivers Heavy Equipment All with 10 yrs or more employm. " " " " " " " 1.3 1.6 1.2 1.7 3.5* 1.6* 1.2 Bus H (l " « Taxi, Chauffeur Mechanics Bus drivers Truck drivers Taxi drivers U " « « « * p < 0.05 CO = Cohort COMMENTS PM = Proportional Mortality N = no; Y = yes « » (l " « 39 Adresses of authors: Professor em. i.TT. Higgins Dept. of Epidemiology School of Public Health University of Michigan Ann Arbor, Ml Dr. R. E. Harris Dept. Preventive Medicine Ohio State University Columbus, OH 43210 Prof. Dr. E. L. Wynder American Health Foundation 320 East 43 Street New York, N.Y. 10017 41 Mitglieder des FAT-AK 1 'Automobil und Umwelt' Dr. rer. nat. Norbert Pelz Mercedes-Benz AG Abt. EP/MVAK 70322 Stuttgart Dr.-Ing. Norbert Metz B M W AG Abt. W-2 80788 München Dr.rer.nat. Helmut König M A N Nutzfahrzeuge AG Abt. TVC-N Postfach 44 0100 90206 Nürnberg Dipl.-Chem. Heiner Winneke Volkswagen AG Abt. E/ZL-UW Postfach 38463 Wolfsburg Dipl.-Ing. Josef Rösgen Pierburg GmbH & Co. KG Abt. T1A 41010 Neuss Dr. rer. nat. H. R. Pfeil Ford Werke AG Abt. NM/IRG-3 50725 Köln Dr.-Ing. H. Kemman Adam Opel AG TEZ-Motorenversuch 65423 Rüsselsheim Dipl.-Ing. Ulrich Dworzak Dr.Ing.h.c.F. Porsche AG Abt. EPL 9 71283 Weissach Dir. Dipl.-Ing. E. Santiago Zeuna Stärker GmbH & Co. KG Entwicklungsleitung 86016 Augsburg Dr. med. M. Spallek Volkswagen AG Gesundheitsschutz 34219 Baunatal Dr.-Ing. Dr.med. H.-G. Grimm Volkswagen AG Zentrales Gesundheitswesen 38463 Wolfsburg Professor Dr.rer.nat. Horst Klingenberg TU 'Otto von Guericke' - Institut f. Maschinenmeßtechnik, Kolbenmaschinen und Instandhaltung 39106 Magdeburg Bisher in der FAT-Schriftenreihe erschienen : Nr. Nr. Nr. Nr. Nr. Nr. Nr. Nr. Nr. Nr. 4 5 6 7 8 9 10 11 12 13 Nr. 14 Nr. Nr. Nr. Nr. Nr. 15 16 17 18 19 Nr. 20 Nr. 21 Nr. 22 Nr. 23 Nr. 24 Nr. 25 Nr. 26 Nr. 27 Nr. 28 Nr. 29 Nr. 30 Nr. 31 Nr. 32 Nr. 33 Nr. 34 Nr. 35 Nr. 36 Nr. 37 Nr. 38 Nr. 39 Nr. 40 Nr. 41 Nr. 42 Nr. 43 Nr. 44 Nr. 45 Nr. 46 Nr. 47 Nr. 48 Nr. 49 Nr. 50 Nr. 51 Nr. 52 Nr. 53 Nr. 54 Nr. 55 Nr. 56 Nr. 57 Nr. 58 Nr. 59 Nr. 60 Nr. 61 Nr. 62 Nr. 63 Nr. 64 Nr. 65 Nr. 66 Nr. 67 Nr. 68 Nr. 69 Nr. 70 Nr. 71 Immissionssituation durch den Kraftverkehr in der Bundesrepublik Deutschland Systematik der vorgeschlagenen Verkehrslenkungssysteme Literaturstudie über die Beanspruchung der Fahrbahn durch schwere Kraftfahrzeuge Unfallforschung/Westeuropäische Forschungsprogramme und ihre Ergebnisse/Eine Übersicht Nutzen/Kosten-Untersuchungen von Verkehrssicherheitsmaßnahmen Belastbarkeitsgrenze und Verletzungsmechanik des angegurteten Fahrzeuginsassen Biomechanik des Fußgängerunfalls Der Mensch als Fahrzeugführer Güterfernverkehr auf Bundesautobahnen Recycling im Automobilbau - Literaturstudie Rückführung und Substitution von Kupfer im Kraftfahrzeugbereich Der Mensch als Fahrzeugführer Stcherheitsmaßnahmen im Straßenverkehr Sammlung, Beschreibung und Auswahl für die Anwendung der Nutzen/Kosten-Analyse Tierexperimentelle und epidemiologische Untersuchungen zur biologischen Wirkung von Abgasen aus Verbrennungsmotoren (Otto- und Dieselmotoren) - Literaturstudie Belastbarkeitsgrenzen des angegurteten Fahrzeuginsassen bei der Frontalkollision Güterfernverkehr auf Bundesautobahnen - Ein Systemmodell, 2. Teil Ladezustandsanzeiger für Akkumulatoren Emission, Immission und Wirkung von Kraftfahrzeugabgasen Sicherheitsmaßnahmen im Straßenverkehr Ergebnisse einer Nutzen/Kosten-Analyse von ausgewählten Maßnahmen Aluminiumverwendung im Automobilbau und Recycling Fahrbahnbeanspruchung und Fahrsicherheit ungelenkter Dreiachsaggregate in engen Kurven Umskalierung von Verletzungsdaten nach AIS - 80 (Anhang zu Schrift Nr. 15) Grundlagen und Möglichkeiten der Nutzung sprachlicher Informationssysteme im Kraftfahrzeug Altteileverwendung im Automobilbau Energie für den Verkehr - Eine systemanalytische Untersuchung der langfristigen Perspektiven des Verkehrssektors in der Bundesrepublik Deutschland und dessen Versorgung mit Kraftstoffen im energiewirtschaftlichen Wettbewerb Wirtschaftlichkeit des Einsatzes von Aluminium im Lkw-Bau Äußere Sicherheit von Lkws und Anhängern Dämpfung und Tilgung von Torsionsschwingungen im Triebstrang von Kraftfahrzeugen Wirkungsgradmessung an Getrieben und Getriebeelementen Fahrverhalten von Lastzügen und hierbei insbesondere von Anhängern Entwicklung, Aufbau und Test eines Ladezustandsanzeigegerätes für Bleiakkumulatoren in Elektrostraßenfahrzeugen Rollwiderstand und Lenkwilligkeit von Mehrachsanhängern mit Zwillings- und Einzelbereifung Fußgängerschutz am Pkw - Ergebnisse mathematischer Simulation Verfahren zur Analyse von Unfallursachen - Definitionen, Erfassung und Bewertung von Datenquellen Untersuchungen über kraftstoffsparende Investitionsmaßnahmen im Straßenbau Belastbarkeitsgrenzen und Verletzungsmechanik der angegurteten Fahrzeuginsassen beim Seitenaufprall. Phase I: Kinematik und Belastungen im Vergleich Dummy/Leiche Konstruktive Einflüsse auf das Fahrverhalten von Lastzügen Studie über Energieeinsparungsgeräte zur Mitführung im Kraftfahrzeug (Bordlader) Grundlagen und Möglichkeiten der Nutzung sprachlicher Informationssysteme im Kraftfahrzeug - Hauptstudie Sprachausgaben im Kraftfahrzeug - Ein Handbuch für Anwender Auswertung von Forschungsberichten über: Die Auswirkung der Nutzfahrzeugkonstruktion auf die Straßenbeanspruchung Fußgängersicherheit - Ergebnisse eines Symposiums über konstruktive Maßnahmen am Auto Auswirkungen der Nutzfahrzeugkonstruktion auf die Straßenbeanspruchung - Gesamtbericht Sprachliche Informationssysteme und Anwendungsmöglichkeiten im Kraftfahrzeug - Ergebnisse eines Symposiums Abgasemissions- und Kraftstoffverbrauchsprognosen für den Pkw-Verkehr in der Bundesrepublik Deutschland im Zeitraum von 1970 bis 2000 auf der Basis verschiedener Grenzwertsituationen Bewertung von Personenverkehrssystemen - Systemanalytische Untersuchungen von Angebotsund Nachfrageelementen einschließlich ihrer Wechselwirkungen Nutzen/Kosten-Analyse für einen Pkw-Frontunterfahrschutz an Nutzfahrzeugen Radlastschwankungen und dynamische Seitenkräfte bei zwillingsbereiften Achsen Studie über die Wirtschaftlichkeit von Verbundwerkstoffen mit Aluminiummatrix im Nutzfahrzeugbau Rechnerische Simulation des dynamischen Verhaltens von nicht stationär betriebenen Antrieben und Antriebselementen Simulationsmodell - Schwingungsprogramm zur Ermittlung der Beanspruchung von Antriebssträngen Verwendung von Kunststoff im Automobil und Wiederverwertungsmöglichkeiten Entwicklung eines hochgenauen, normfähigen Verfahrens zur Wirkungsgradmessung an Antriebselementen Erhebung und Auswertung von Straßenverkehrsunfalldaten in der Bundesrepublik Deutschland Ergebnisse eines VDA/FAT-Fachgesprächs Untersuchungen zur subakuten und chronischen Wirkung von Ottomotorabgasen auf den Säugetierorganismus Pilotzelle zur Steuerung von Batterien in Fahrzeugen mit Elektro- oder Elektro-Hybrid-Antrieb Wirkungen von Automobilabgas und seiner Inhaltsstoffe auf Pflanzen - Literaturstudie Rekonstruktionen von fünf realen Seitenkollisions-Unfällen - Ergänzende Auswertung der KOB-Daten Luftqualität in Fahrgasträumen Belastbarkeitsgrenzen und Verletzungsmechanik des angegurteten Pkw-Insassen beim Seitenaufprall Phase II: Ansätze für Verletzungsprädiktionen Erhebung und Analyse von Pkw-Fahrleistungsdaten mit Hilfe eines mobilen Datenerfassungssystems - Methodische und meßtechnische Ansätze für eine Pilotstudie Technische Erfahrungen und Entwicklungsmöglichkeiten bei Sicherheitsgurten im Fond von Pkw - Ergebnisse eines Symposiums Untersuchungen über Wirkungen von Automobilabgas auf pflanzliche Bioindikatoren im Umfeld einer verkehrsreichen Straße in einem Waldschadensgebiet Sicherheitsorientierte Bewertung von Anzeige- und Bedienungselementen in Kraftfahrzeugen - Grundlagen Quantifizierung der Radlastdynamik bei Einfach-, Doppel- und Dreifachachsen in Abhängigkeit vom Federungs- und Dämpfungssystem des Fahrzeugs Seitenverkleidung am Lkw - Technische Analyse Vorstudie für die Durchführung von Tracermessungen zur Bestimmung von Immissionskonzentrationen durch Automobilabgase Untersuchung fahrdynamischer Eigenschaften kurzgekuppelter Lastzüge bei Kursänderungen Abschlußbericht der Pilotstudie zum Fahrleistungspanel „Autofahren in Deutschland" Herstellung und Analyse charakteristischer Abgaskondensate von Verbrennungsmotoren für die Untersuchung ihrer biologischen Wirkung bei nichtinhalativen Tests Bewertung von Personenverkehrssystemen Teil II: Auswirkungen aus Angebots- und Nachfrageänderungen im Personenverkehr vergriffen DM 20,DM 30,vergriffen DM 60,DM 50,DM 30,vergriffen DM 50,DM 50,DM 50,DM 50,DM 60,- DM DM DM DM DM 60,50,50,50,30,- vergriffen DM 50,DM 50,DM 50,DM 50,DM 50,- DM DM DM DM DM DM 60,50,60,50,50,50,- DM DM DM DM DM 50,60,60,75,75,- DM 60,DM 50,DM 30,DM DM 60,25,- DM DM DM 30,30,20,- DM 30,- DM 50,- vergriffen DM 30,DM 40,DM 50,DM 250,DM 275,vergriffen DM 160,DM 50,- DM DM DM DM DM 75,40,30,35,50,- DM 95,- DM 35,- DM 60,- DM 95,vergriffen DM DM 30,50,- DM 30,DM 85,DM 85,DM 55,- DM 65,- Bisher in der FAT-Sch ritten reihe erschienen: Nr Nr. 73 74 Nr. 75 76 Nr Nr 79 Nr 80 Nr. 81 Nr. 82 Nr 83 Nr. 84 Nr 85 Nr. 86 Nr. 87 Nr 88 Nr 89 Nr 90 Nr. 91 Nr 92 Nr Nr Nr Nr Nr Nr Nr 93 94 95 96 97 98 99 Nr Nr. Nr Nr 100 101 102 103 Nr 104 Ni 105 Nr 106 Nr 107 Nr 108 Nr 109 Nr. 110 Nr. 111 Untersuchung über das Emissionsverhalten der Leichtmüllfraktion aus Autoshredderanlagen beim Verbrennen Verletzungsfolgekosten nach Straßenverkehrsunfällen Sicherheitsorientierte Bewertung von Anzeige- und Bedienelementen in Kraftfahrzeugen - Empirische Ergebnisse Retrospektive Untersuchung über die innere Sicherheit von Lkw-Fahrerhäusern Aufbau und Labortest eines wartungsarmen, sich selbst überwachenden Batterieaggregates für Strafîenfahrzeuge mit Elektro- und Elektro-Hybrid-Antrieb - Vorbereitende Untersuchungen Belastungsgrenze und Verletzungsmechanik des angegurteten Pkw-Insassen beim 90 -Seitenaufprall Phase III: Vertiefende Analyse der überarbeiteten und zum Teil neu berechneten HeidelbergerSeitenaufprall-Daten Ermittlung von ertragbaren Schnittkräften für die betriebsfeste Bemessung «on Punktschweißverbindungen im Automobilbau Verhalten des EUROSID beim 90°-Seitenaufprall im Vergleich zu PMTO sowie US-SID, HYBRID II und APROD Demontagefreundliche Gestaltung von Automobilien - Teil I Grundlagenuntersuchung zum Einfluß der Sonneneinstrahlung auf die thermische Behaglichkeit in Kraftfahrzeugen Einsatz von Retardern in der Betriebsbremsanlage von Nutzfahrzeugen - Zweiachsiges Fahrzeug Zwei Bände Belastungen und Verhalten des EUROSID bei unterschiedlichen Prüfverfahren zum Seitenaufprall Kosten einer kontinuierlichen Pkw-Fahrleistungserhebung Auswirkungen der Nutzfahrzeugkonstruktion auf die Straßenbeanspruchung Seitenkräfte an Mehrfachachsen von Sattelanhängern bei Kurvenfahrt und durch Spurrinnen Verfahren zur Umwandlung polymerer Mischabfälle aus der Autositz-Produktion in Polyole Methoden zur Vorausberechnung der Faserorientierung beim Pressen von SMC mit geschnittenen Glasfasern Teil I: Unverrippte Bauelemente Teil II: Verrippte Bauelemente Fahrzeugerprobung eines wartungsarmen Batterieaggregates Grundsatzuntersuchungen zum Festigkeitsverhalten von Durchsetzfügeverbindungen aus Stahl Fahrverhalten von Lkw mit Zentralachsanhängern Der Fahrer als adaptiver Regler Einfluß realer Betriebsverhältnisse auf die Reproduzierbarkeit von Wirkungsgradbestimmungen an nicht stationär betriebenen Getrieben Mobilität - Automobil - Energiebedarf Rationalisierungspotentiale im Straßenverkehr I Abschlußbericht „Einsatz von Retardern in der Betriebsbremsanlage von zweigliedrigen Lastzügen" Vermessung des 50%-Hybrid III Dummy zur Ermittlung eines verbesserten Datensatzes für Crashsimulationen Erfassung des Wissensstandes über Reifen-/Fahrbahngeräusche beim Nutzfahrzeug Zusammenhang zwischen Wetterbedingungen und Verkehrsunfällen Untersuchung von Unternehmensstrukturen und Bestimmung der technischen Leistungsfähigkeit moderner Altautoverwerterbetriebe Demontage und Verwertung von Kunststoffbauteilen aus Automobilen Die elektromagnetische Umwelt des Kraftfahrzeugs Einfluß der Zerspanung auf die Bauteilbetriebsfestigkeit unter Berücksichtigung des Hartdrehens Vermessung von 5°/o-, 95%-Hybrid III und US-SID Dummies zur Ermittlung von Datensätzen für Crashsimulationen Antriebe für Elektrostraßenfahrzeuge Einsatz von Retardern in der Betriebsbremsanlage von dreigliedrigen Lastzügen Festigkeits- und Steifigkeitsverhalten von dünnen Blechen mit Sicken Frontunterfahrschutz an Lkw Bewertung der Aussagefähigkeit von Seitenaufprallversuchen mit Ganzfahrzeugen Einfluß der Sonneneinstrahlung auf die thermische Behaglichkeit in Kraftfahrzeugen Schädigungsmechanismen bei kreuzverzahnten Flanschverbindungen Ermittlung ertragbarer Beanspruchungen am Schwerpunkt auf Basis der übertragenen Schnittgrößen Bewertung epidemiologischer Untersuchungen über Dieselmotorabgas und Lungen- und Blasenkrebs vergriffen DM 90,- DM 85 DM 90 vergriffi DM 50 DM 110 DM 85 DM 45 DM 40 DM 30 DM DM DM DM DM 85 45 65 65 85 DM DM DM DM DM DM DM 60 85 75 70 25 50 50 DM DM DM DM 35 50 170 95 DM DM DM DM DM DM DM 30 60 40 95 45 35 85 DM320 DM380 DM 25